444 - QTc Comparison Between Neonates with Neonatal Opioid Withdrawal Syndrome and Healthy Non-Opioid Exposed Neonates

Publication Number: 444.6199

Kevin Lam, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, United States; Gary Peltz, Stanford University School of Medicine, Stanford, CA, United States; Walter k. Kraft, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, United States

Background: While neonates may be at risk for long QT syndrome, interpreting neonate electrocardiograms (ECGs) is challenging given the immense variability within the first week of life. While ECGs are not typically done, one clinical trial observed no statistically significant difference in the mean QTc between neonates with neonatal opioid withdrawal syndrome (NOWS) receiving ondansetron or placebo five days post-delivery.

Objective: Explore the variability in observed QTc values between neonates with NOWS compared to healthy, non-opioid exposed neonates.

Design/Methods: Daily QTc Bazett values for neonates with NOWS were already collected as part of a published clinical trial (NCT01965704). All except preterm neonates (i.e., before 37 0/7 weeks) were included in the analysis regardless of treatment allocation and the number of study doses received. Daily QTc values for up to five days post-delivery were summarized using descriptive statistics with R version 4.4.1. Reference data were reported in a published study assessing the relationship between gestational age and neonatal ECG parameters (PMID: 34814190). Observed and reference QTc values were stratified by gestational age (GA) designations.

Results: 86 neonates were included in the analysis after excluding those who did not meet the inclusion criteria, did not receive any study drug, or withdrew from the parent NOWS trial. Almost all neonates with NOWS were either early or full term, but all were within the reference ranges (Table 1). Except for screening, all QTc values up to the third prespecified safety follow-up ECG for each neonate with NOWS were included in the analysis. For neonates with NOWS, the variability in QTc was generally the greatest during the first day of life but decreases with age (Figure 1). Overall, median QTc values were somewhat variable after accounting for GA but not sex. The effect of late term pregnancy on daily QTc is not shown as there was only one neonate. While the median QTc values for neonates with NOWS were similar to the reference, these were associated with a wider spread (Table 2).

Conclusion(s): QTc is the highest and has the most variability in the first day of life before stabilizing with age for neonates with NOWS. GA may have an effect on QTc within the first week of life, but not sex. NOWS may contribute more variability to QTc compared to healthy neonates, which may be due to the enhanced noradrenergic state.

Table 1. Demographics
Adapted from Hartmann J, Pærregaard MM, Norsk J, et al. Gestational Age and Neonatal Electrocardiograms. Pediatrics. 2021;148(6):e2021050942.

Figure 1. QTc Bazett for neonates with NOWS by gestational age and sex


Table 2. QTc Bazett values stratified by gestational age designations
Adapted from Hartmann J, Pærregaard MM, Norsk J, et al. Gestational Age and Neonatal Electrocardiograms. Pediatrics. 2021;148(6):e2021050942. Data are shown as median (2nd – 98th percentiles). * Only one neonate was born late term.